Abstract：
UNASSIGNED: Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM.
UNASSIGNED: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo).
UNASSIGNED: Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p < 0.01; I2 = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p < 0.01; I2 = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p < 0.01; I2 = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; p < 0.01; I2 = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; p < 0.01; I2 = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; p = 0.105; I2 = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; p < 0.01; I2 = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; p = 0.792; I2 = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction.
UNASSIGNED: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention.
UNASSIGNED: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo).
UNASSIGNED: Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p < 0.01; I2 = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p < 0.01; I2 = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p < 0.01; I2 = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; p < 0.01; I2 = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; p < 0.01; I2 = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; p = 0.105; I2 = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; p < 0.01; I2 = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; p = 0.792; I2 = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction.
UNASSIGNED: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention.
摘要：
■大量证据表明，胰高血糖素样肽-1受体激动剂（GLP-1RA）可降低2型糖尿病（T2DM）的心血管风险。Tirzepatide是一流的，双重葡萄糖依赖性促胰岛素多肽GIP/GLP-1RA被批准用于T2DM。
■对随机对照临床试验（RCT）进行了系统评价和荟萃分析，以评估：（i）主要不良心血管事件（MACE）的发生率；（ii）中风的发生率，致命的,使用GLP-1或GIP/GLP-1RAs治疗的T2DM患者的非致死性卒中（与安慰剂相比）。
■13项随机对照试验（9项和4项关于GLP-1RA和替拉帕肽，分别）包括65,878名T2DM患者。与安慰剂相比，GLP-1RAs或GIP/GLP-1RAs可降低MACE(OR:0.87;95%CI:0.81-0.94;p<0.01;I2=37%),全因死亡率(OR:0.88;95%CI:0.82-0.96;p<0.01;I2=21%)和心血管死亡率(OR:0.88;95%CI:0.80-0.96;p<0.01;I2=14%),GLP-1与GIP/GLP-1RA之间没有差异。此外,GLP-1RA降低了卒中（OR：0.84;95％CI：0.76-0.93;p<0.01;I2=0％）和非致死性卒中（OR：0.85;95％CI：0.76-0.94;p<0.01;I2=0％）的几率，而未发现致命性卒中与GLP-1RAs之间的关联(OR:0.80;95%CI:0.61-1.05;p=0.105;I2=0%).在二级分析中，GLP-1RA可预防缺血性卒中(OR:0.74;95%CI:0.61-0.91;p<0.01;I2=0%)和MACE复发,而非出血性卒中(OR:0.92;95%CI:0.51-1.66;p=0.792;I2=0%)。GLP-1RAs或GIP/GLP-1RAs与致死性或非致死性心肌梗死之间无关联。
■GLP-1和GIP/GLP-1RA可降低T2DM的心血管风险和死亡率。虽然有确凿的证据表明GLP-1RA显著降低T2DM患者缺血性卒中的风险，需要专门的RCTs来评估新型GIP/GLP-1RA用于初级和二级卒中预防的有效性.
■对随机对照临床试验（RCT）进行了系统评价和荟萃分析，以评估：（i）主要不良心血管事件（MACE）的发生率；（ii）中风的发生率，致命的,使用GLP-1或GIP/GLP-1RAs治疗的T2DM患者的非致死性卒中（与安慰剂相比）。
■13项随机对照试验（9项和4项关于GLP-1RA和替拉帕肽，分别）包括65,878名T2DM患者。与安慰剂相比，GLP-1RAs或GIP/GLP-1RAs可降低MACE(OR:0.87;95%CI:0.81-0.94;p<0.01;I2=37%),全因死亡率(OR:0.88;95%CI:0.82-0.96;p<0.01;I2=21%)和心血管死亡率(OR:0.88;95%CI:0.80-0.96;p<0.01;I2=14%),GLP-1与GIP/GLP-1RA之间没有差异。此外,GLP-1RA降低了卒中（OR：0.84;95％CI：0.76-0.93;p<0.01;I2=0％）和非致死性卒中（OR：0.85;95％CI：0.76-0.94;p<0.01;I2=0％）的几率，而未发现致命性卒中与GLP-1RAs之间的关联(OR:0.80;95%CI:0.61-1.05;p=0.105;I2=0%).在二级分析中，GLP-1RA可预防缺血性卒中(OR:0.74;95%CI:0.61-0.91;p<0.01;I2=0%)和MACE复发,而非出血性卒中(OR:0.92;95%CI:0.51-1.66;p=0.792;I2=0%)。GLP-1RAs或GIP/GLP-1RAs与致死性或非致死性心肌梗死之间无关联。
■GLP-1和GIP/GLP-1RA可降低T2DM的心血管风险和死亡率。虽然有确凿的证据表明GLP-1RA显著降低T2DM患者缺血性卒中的风险，需要专门的RCTs来评估新型GIP/GLP-1RA用于初级和二级卒中预防的有效性.
